A novel tetrahydrocarbazole derivative-based lysosome-targeted fluorescent probe for the detection of apoptosis and polarity change in biological system.

Apoptosis is accompanied by dynamic alterations in lysosomal microenvironmental parameters including polarity; therefore, real-time monitoring of these changes is essential for elucidating apoptotic mechanisms. Herein, a tetrahydrocarbazole-based fluorescent probe TC-AP-ID with a D-π-A structure was rationally designed and synthesized for polarity detection. The probe exhibited a remarkable solvatochromic effect: the maximum emission wavelength was red-shifted from 606 nm to 653 nm as the 1,4-dioxane/water ratio decreased from 99/1 to 1/99 (v/v), accompanied by a gradual decrease in fluorescence intensity. The probe demonstrated excellent emission stability over a wide pH range of 3-11. Colocalization experiments with Lyso-Tracker Green in HeLa cells yielded a high Pearson correlation coefficient of 0.95. The probe successfully realized real-time imaging of apoptosis induced by cisplatin (0-50 μM) and polarity changes during H2O2-mediated oxidative stress in live HeLa cells and zebrafish larvae. These findings indicated that probe TC-AP-ID was an effective tool for investigating lysosomal microenvironmental alteration in apoptotic progression and drug-induced cytotoxicity.